Paroxysmal sympathetic hyperactivity: An entity to keep in mind

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Source: Hughes and Rabinstein.<a class="elsevierStyleCrossRef" href="#bib0255">8</a>" ] ] ] "textoCompleto" => "IntroductionIn 1929 Wilder Penfield described the case of a 41-year-old woman who developed sudden and paroxysmal arterial hypertension, tachycardia and tachypnea with occasional changes from normal ventilation toward Cheyne-Stokes respiration.<a class="elsevierStyleCrossRef" href="#bib0220">1</a> During the paroxysmal episodes the body temperature was seen to rise, with intermittent dilatation and contraction of the pupils, and excessive tearing.<a class="elsevierStyleCrossRef" href="#bib0220">1</a> The patient presented a third ventricle cholesteatoma. Penfield referred to these episodes as “diencephalic autonomic epilepsy”, and suggested that they reflected hyperactivity of both the sympathetic and the parasympathetic autonomic nervous system.<a class="elsevierStyleCrossRef" href="#bib0220">1</a>Since this first publication there have been reports of similar conditions in many types of serious brain injuries, and different terms have been used to describe them.<a class="elsevierStyleCrossRefs" href="#bib0225">2–6</a> Sympathetic alterations predominate in some cases and parasympathetic alterations in others, though both the sympathetic and the parasympathetic autonomic nervous system can be more or less equally affected in some patients. This circumstance tends to cause confusion, making it difficult to adequately study the disease<a class="elsevierStyleCrossRefs" href="#bib0225">2,6</a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>The term “paroxysmal sympathetic hyperactivity” (PSH) has recently been introduced, summarizing the main characteristics of the syndrome, which results from overactivity of only the sympathetic nervous system.<a class="elsevierStyleCrossRefs" href="#bib0225">2–5,7,8</a>Paroxysmal sympathetic hyperactivity is a genuine neurological emergency that may go undetected if not taken into account.<a class="elsevierStyleCrossRefs" href="#bib0225">2–8</a> The diagnosis is mainly established on an exclusion basis, ruling out other possible diagnoses, and requires a strong degree of suspicion. Failure to adequately detect and treat the condition is associated to high mortality-morbidity rates.<a class="elsevierStyleCrossRefs" href="#bib0225">2–5</a>The main objective of this study is to offer simple and practical answers to questions referred to the correct identification and management of the disease.Question 1. What do we mean by paroxysmal sympathetic hyperactivity?Paroxysmal sympathetic hyperactivity comprises a series of signs and symptoms reflecting exacerbated sympathetic activity, including: tachycardia, arterial hypertension, tachypnea, hyperthermia, generalized perspiration, anomalous motor activity (dystonia, muscle stiffness, extension) and mechanical ventilator maladjustment.<a class="elsevierStyleCrossRefs" href="#bib0225">2–8</a> These clinical features moreover manifest simultaneously.<a class="elsevierStyleCrossRefs" href="#bib0225">2–8</a> The number of signs or symptoms is closely correlated to the ultimate outcome,<a class="elsevierStyleCrossRef" href="#bib0235">4</a> with more profuse manifestations being associated to a poorer prognosis.<a class="elsevierStyleCrossRef" href="#bib0235">4</a>Paroxysmal sympathetic hyperactivity is not a primary disorder but always develops as a result of brain injuries of variable nature and severity.<a class="elsevierStyleCrossRefs" href="#bib0225">2–8</a>Question 2. What are the main characteristics of paroxysmal sympathetic hyperactivity?Paroxysmal sympathetic hyperactivity manifests abruptly in cyclic episodes, either spontaneously or in response to stimuli such as pain, bathing, the aspiration of secretions, exposure to light, touch or physiotherapy.<a class="elsevierStyleCrossRefs" href="#bib0225">2–8</a> Sympathetic hyperactivity can manifest at any time in the course of the disorder that causes it, though it is usually detected after the first week, coinciding with a decrease or the suspension of deep sedoanalgesia<a class="elsevierStyleCrossRefs" href="#bib0225">2–8</a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The literature indicates that in most instances the diagnosis is made one week after patient admission.<a class="elsevierStyleCrossRef" href="#bib0255">8</a> The paroxysms appear 3–5 times a day and last an average of 30min.<a class="elsevierStyleCrossRefs" href="#bib0225">2–8</a><elsevierMultimedia ident="fig0005"></elsevierMultimedia>The syndrome has three evolutive stages.<a class="elsevierStyleCrossRef" href="#bib0255">8</a> Hyperacute phase I covers the first week, during which the expression of brain damage is maximum. The patient is generally unstable and intensive treatment is provided, including generally deep sedation and analgesia. As a result, the diagnosis cannot be established in this stage, unless a waking test is made for some reason or the patient accidentally emerges from anesthesia.<a class="elsevierStyleCrossRef" href="#bib0255">8</a> In phase II the syndrome – with the aforementioned features – is fully expressed. This stage typically extends to two and a half months after the causal injury (day 74).Cessation of the perspiration episodes marks the end of stage II,<a class="elsevierStyleCrossRef" href="#bib0255">8</a> which is followed by stage III. The latter comprises the rehabilitation period and can last for years – though the episodes in this case are generally less frequent and of lesser intensity and duration<a class="elsevierStyleCrossRef" href="#bib0255">8</a> (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Question 3. What is the incidence and what are the disorders predisposing to paroxysmal sympathetic hyperactivity?The reported incidence of PSH ranges from 8% to 33%,<a class="elsevierStyleCrossRefs" href="#bib0225">2–8</a> depending on the series and the underlying etiology of the disease. The disease can manifest in both children and adults,<a class="elsevierStyleCrossRefs" href="#bib0225">2–8</a> and has no particular age or gender predilection. A number of conditions predispose to the development of PSH, the most common being traumatic brain injury (80%) in its diffuse axonal damage presentation,<a class="elsevierStyleCrossRefs" href="#bib0260">9–14</a> followed by post-cardiac arrest anoxic-ischemic encephalopathy (10%) and cerebrovascular accident (CVA) (5.5%).<a class="elsevierStyleCrossRefs" href="#bib0225">2–8</a> In relation to CVA, spontaneous intraparenchymal bleeding of the basal nuclei, thalamus and cerebellar vermis, with or without ventricular collapse, is seen to predominate.<a class="elsevierStyleCrossRefs" href="#bib0290">15,16</a> There have also been reports of PSH in patients with severe subarachnoid hemorrhage,<a class="elsevierStyleCrossRefs" href="#bib0300">17,18</a> ischemic CVA, cerebral venous thrombosis, encephalitis and cerebral lipid embolism<a class="elsevierStyleCrossRefs" href="#bib0225">2–5,19,20</a> (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).<elsevierMultimedia ident="fig0015"></elsevierMultimedia>Question 4. What are the physiopathological bases of paroxysmal sympathetic hyperactivity?The main intervening element is the autonomic nervous system (ANS) or neurovegetative system, which is in charge of regulating involuntary actions through its three main components: sympathetic, parasympathetic and enteric.<a class="elsevierStyleCrossRef" href="#bib0320">21</a> The ANS is essentially an efferent system. It receives information from the internal environment, glands and organs through a complex network located in the spinal cord, brainstem, diencephalon, hypothalamus, limbic system and certain areas of the brain cortex, and subsequently transmits impulses toward the periphery.<a class="elsevierStyleCrossRef" href="#bib0320">21</a> In this way the ANS regulates heart rate, respiratory frequency, pupil diameter and blood vessel caliber, smooth muscle contraction, salivation, perspiration, sexual function, endocrine and exocrine gland secretion, and digestion.<a class="elsevierStyleCrossRef" href="#bib0320">21</a>The sympathetic nervous system is composed of preaortic and pre- and paravertebral ganglionic networks. Catecholamines are the main intervening neurotransmitters, and are carefully regulated and balanced through excitatory and inhibitory impulses.<a class="elsevierStyleCrossRef" href="#bib0320">21</a> When this balance is altered as a consequence of brain damage, catecholamine release becomes excessive, thereby giving rise to the clinical features typical of PSH.<a class="elsevierStyleCrossRefs" href="#bib0325">22,23</a>Why do imbalances resulting in catecholamine elevation during sympathetic paroxysm occur? The precise underlying physiopathology remains unclear. The syndrome was initially attributed to seizures or endocranial hypertension. Both conditions were discarded, however, since there is no close correlation between these two disorders and the presence of the syndrome.<a class="elsevierStyleCrossRefs" href="#bib0225">2–5,24,25</a> The absence of seizure activity as evidenced by the electroencephalogram (EEG) during sympathetic paroxysms has been clearly confirmed.<a class="elsevierStyleCrossRefs" href="#bib0225">2,24,25</a> On the other hand, a rise in intracranial pressure (ICP) is more a consequence than a cause of the syndrome.<a class="elsevierStyleCrossRefs" href="#bib0225">2–5</a>Following brain damage there is an immediate metabolic and inflammatory response, with activation of the ANS.<a class="elsevierStyleCrossRef" href="#bib0345">26</a> This in turn induces tachycardia, arterial hypertension and the redistribution of blood flow toward the brain, heart and adrenal glands, in order to ensure the availability of oxygen and preserve the physiological functions of the vital organs of the body. The parasympathetic system in turn attempts to restore homeostasis by reducing the effects of sympathetic hyperactivity. However, when this parasympathetic feedback mechanism fails, sympathetic activity is disinhibited, hyperactivity results, and PSH ultimately develops. Two hypotheses have been proposed to explain this phenomenon<a class="elsevierStyleCrossRefs" href="#bib0335">24,25</a> (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).<elsevierMultimedia ident="fig0020"></elsevierMultimedia>The conventional theory of disconnection – whether structural (anatomical lesion) or functional (imbalanced neurotransmitter release) – postulates that sympathetic excitatory centers located in the diencephalon and upper region of the brainstem become freed from higher cortical-subcortical control.<a class="elsevierStyleCrossRef" href="#bib0335">24</a>The excitation-inhibition ratio model in turn postulates that the centers located in the brainstem and diencephalon are inhibitory by nature. In this respect, they limit amplification and sensitization of the afferent sensory information coming from the spinal cord.<a class="elsevierStyleCrossRefs" href="#bib0335">24,25</a> In this model, PSH is referred to as allodynia – a term that defines a sensitization process occurring in the dorsal horn of the spinal cord, in which non-painful stimuli are perceived as painful, including the aspiration of secretions, body rotation, bathing, constipation and urinary retention.<a class="elsevierStyleCrossRefs" href="#bib0335">24,25</a> At the same time, painful stimuli become magnified in intensity.On the other hand, the excitation-inhibition ratio model helps explain the triggering of PSH in response to environmental stimuli, as well as the response to drugs used to control the disorder.<a class="elsevierStyleCrossRefs" href="#bib0335">24,25</a>Question 5. How can a correct diagnosis be established?A strong degree of suspicion is required, particularly when in the context of acquired brain damage, during therapeutic de-escalation, “awakening from coma”, or in the rehabilitation phase, the patient suffers simultaneous and transient paroxysmal episodes of sympathetic hyperactivity.<a class="elsevierStyleCrossRefs" href="#bib0225">2,3,6–8,27</a>The predominant signs and symptoms are: tachycardia (98%), arterial hypertension (72%), excessive perspiration (79%), fever in the absence of an infectious focus (79%), tachypnea (85%), extensor body posture (38%), dystonia (38%), stiffness or spasticity (44%). Less frequent manifestations are: intermittent dilation of the pupils, diminished consciousness, hair erection, excitation and mechanical ventilator maladjustment.<a class="elsevierStyleCrossRefs" href="#bib0225">2,8</a>No complementary tests are available for confirming the diagnosis of PSH. The diagnosis is eminently clinical, and other situations involving similar clinical features therefore need to be ruled out<a class="elsevierStyleCrossRefs" href="#bib0225">2,3,6–8</a> (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Although the syndrome has been known for over 60 years, its diagnostic criteria are not homogeneous and have not been validated.<a class="elsevierStyleCrossRefs" href="#bib0225">2–8</a> Different numbers and combinations of signs have been used to confirm the existence of PSH,<a class="elsevierStyleCrossRefs" href="#bib0225">2,28</a> and only recently has expert consensus established its definition and the criteria to be used.<a class="elsevierStyleCrossRef" href="#bib0360">29</a> Following a systematic review of the literature, a scale was developed based on the combination of a score that assesses the presence and severity of the clinical parameters (Clinical Features Severity [CFS]). This score is added to another score that assesses the characteristics of the episodes (frequency, duration, persistence over time, simultaneity, etc.), known as the Diagnosis Likelihood Tool (DLT)<a class="elsevierStyleCrossRefs" href="#bib0360">29,30</a> (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). The final score obtained from the sum of these two scales allows us to calculate the probability of suffering PSH with increased precision, though its validation remains pending.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Although the catecholamine or other hormonal axis values for diagnosing the syndrome have not been defined, a recent study has generated the first proof of catecholamine elevation and, to a lesser extent, increased adrenocortical response, in individuals with PSH versus controls without the syndrome.<a class="elsevierStyleCrossRef" href="#bib0330">23</a> These findings provide bases for warranting the current nomenclature referred to the disease.<a class="elsevierStyleCrossRef" href="#bib0360">29</a>Question 6. Is neuroimaging necessary?Neuroimaging is not essential for diagnosing PSH. Nevertheless, it contributes to maintain a high level of suspicion by revealing the type of brain injury in the initial imaging study (focal or diffuse), its morphology (intracerebral hemorrhage, ischemia, contusions, extraaxial hematomas, etc.), the anatomical location, and the extent of the primary damage.<a class="elsevierStyleCrossRefs" href="#bib0370">31–33</a>Computed tomography (CT) is undoubtedly the imaging tool of choice in the acute phase. In more stable patients, without a need for multiple monitoring procedures, magnetic resonance imaging (MRI) with or without tractography can be used to more precisely define the degree of anatomical involvement – particularly as regards those anatomical structures more closely related to the development of PSH.<a class="elsevierStyleCrossRef" href="#bib0385">34</a>Question 7. How should the syndrome be treated?Preventing PSH would be the ideal strategy. However, to date no measures in this regard have been successful. A recent retrospective study with important methodological limitations has indicated that the use of dexmedetomidine, versus the traditionally used sedatives (midazolam or propofol), in brain trauma patients subjected to surgery could reduce the incidence of PSH.<a class="elsevierStyleCrossRef" href="#bib0390">35</a>As in any neurological emergency, the first aim of management is to ensure cardiorespiratory stability by means of the ABC of resuscitation in combination with the measures needed to detect and correct secondary lesions.<a class="elsevierStyleCrossRefs" href="#bib0225">2–5,36–39</a> Adequate nutrition and a correct water-electrolyte balance are very important assisting measures in patients with PSH.<a class="elsevierStyleCrossRef" href="#bib0410">39</a>The existing drug strategies for the specific management of PSH are fundamented upon case series, most of which are retrospective and non-randomized. The quality of the evidence on the efficacy of the proposed measures is therefore poor. Likewise, it is important to note the lack of studies demonstrating the preference of one drug substance versus another. Nevertheless, the experience and the literature indicate that “drug combinations” are generally required, and that these should be evaluated through the so-called “trial and error” approach.<a class="elsevierStyleCrossRefs" href="#bib0230">3,5,20,36,38</a>In order to control excessive sympathetic activity or its consequences, it is important to orientate treatment according to the currently accepted physiopathology of PSH. In this regard, the paroxysms can be mitigated through three main approaches: (a) inhibition of central sympathetic flow; (b) inhibition of afferent sensory processes (preventing the development of allodynia); and (c) blockade of effector organ end response.<a class="elsevierStyleCrossRefs" href="#bib0230">3,5,20,36–38</a>At present, optimized treatment (effectiveness – adverse reactions – interactions) (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>) seeks the following:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">1)Abort crises or suspend symptoms: The aim here is to control the episode immediately in order to prevent adverse effects such as cardiac overload, arrhythmias, dehydration, muscle loss, contractures or delayed recovery from contributing to increase patient morbidity. The drugs used are characterized by rapid onset of action and a short half-life, and the choice of substance depends on the dominant symptom in each case. The indicated drugs include morphine, propranolol and short-acting benzodiazepines.<a class="elsevierStyleCrossRefs" href="#bib0230">3,5,20,36–38</a></li><li class="elsevierStyleListItem" id="lsti0010">2)Prevention of paroxysms: Treatment in this regard seeks to reduce the frequency, duration and intensity of the symptoms, and is indicated in combination with the aforementioned therapy. The drugs used include nonselective beta-blockers (propranolol), α2-agonists (clonidine and dexmedetomidine in some groups of patients<a class="elsevierStyleCrossRef" href="#bib0390">35</a>), bromocriptine, baclofen, gabapentin and long-acting benzodiazepines.<a class="elsevierStyleCrossRefs" href="#bib0395">36,37</a></li><li class="elsevierStyleListItem" id="lsti0015">3)Refractory PSH: When sympathetic hyperactivity persists despite the abovementioned treatments, with the risk of causing secondary brain damage, brain edema, lung edema, myocardial infarction, or catecholaminergic myocarditis including sudden death, use is made of drugs in continuous intravenous infusion, such as benzodiazepines, propofol, opioids or dexmedetomidine.<a class="elsevierStyleCrossRef" href="#bib0405">38</a></li></ul><elsevierMultimedia ident="tbl0020"></elsevierMultimedia>The effective clinical management of patients with PSH requires a clear understanding of the available treatment options, their efficacy, dosing characteristics, half-life, administration route, interactions and adverse effects. Treatment protocolization is therefore essential. A number of algorithms have been published in this respect.<a class="elsevierStyleCrossRefs" href="#bib0230">3,40</a>Since on one hand not all paroxysms are the same in terms of severity, frequency or duration, and on the other hand the available drug substances are not without potential toxic effects, we consider it important to categorize the episodes in order to use the treatment combination offering the best risk-benefit ratio. We thus recommend using the CFS+DLT diagnostic scale and classifying the patients into four possible groups (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>):<elsevierMultimedia ident="fig0025"></elsevierMultimedia>Group A < 8 points. Treatment targeted to the dominant symptom.Group B 8–16 points. Symptomatic+preventive treatment.Group C > 17 points. Symptomatic+preventive treatment+gabapentin or dantrolene or baclofen.Refractory group: Continuous intravenous infusion of propofol, fentanil, midazolam or dexmedetomidine.Question 8. What are the consequences of a lack of diagnosis or adequate management?Paroxysmal sympathetic hyperactivity episodes can be intense and prolonged, and can occur several times a day.<a class="elsevierStyleCrossRefs" href="#bib0225">2–6,41</a> The number of symptoms rather than the duration of PSH is the most important severity indicator.<a class="elsevierStyleCrossRef" href="#bib0235">4</a> Arterial hypertension, fever, hypoxemia, hypercapnia and hyperglycemia can cause secondary brain damage, and are the main causes of a poor prognosis.<a class="elsevierStyleCrossRefs" href="#bib0225">2–6</a> Paroxysmal sympathetic hyperactivity in turn induces a hypermetabolic state, with hypercatabolism and inflammation, and increased vulnerability to infections, sepsis and weight loss, which in turn are associated to increased morbidity, longer hospital stay and slower recovery.<a class="elsevierStyleCrossRefs" href="#bib0225">2–6,20</a> The marked and sustained increase in catecholamine levels predisposes to the development of myocardiopathy, lung edema, arrhythmias, and cardiac and multisystemic dysfunction.<a class="elsevierStyleCrossRefs" href="#bib0225">2–8,20</a> An early diagnosis and optimized treatment of PSH are crucial in order to facilitate patient recovery and avoid permanent disabilities secondary to heterotopic ossification, spastic stiffness, body malpositioning and profound neurocognitive disturbances.<a class="elsevierStyleCrossRefs" href="#bib0225">2–8,20</a> The early start of specific symptoms therapy is believed to reduce the complications rate, shorten stay in the Intensive Care Unit (ICU) and facilitate recovery.<a class="elsevierStyleCrossRef" href="#bib0305">18</a>Diagnostic and/or therapeutic delays in PSH can have devastating consequences for patient recovery. However, on comparing the post-rehabilitation course of patients with and without PSH, functional condition at discharge shows no statistically significant differences as determined from the Functional Independence Measure, Disability Rating Scale and Glasgow Outcome Scale – though the probability and degree of recovery is greater in those without PSH.<a class="elsevierStyleCrossRefs" href="#bib0425">42,43</a>The expectable course of recovery from traumatic brain damage extends from acute management to rehabilitation and reinsertion in the community. The effects of PSH can alter the course of rehabilitation and delay or impede maximum patient recovery.<a class="elsevierStyleCrossRef" href="#bib0430">43</a>Conclusions and future challengesParoxysmal sympathetic hyperactivity is a genuine and potentially fatal neurological emergency. The diagnosis is based on the clinical findings; as a result, the professionals in charge of the care of neurocritical patients must be able to detect the syndrome and require adequate training. The greatest challenge in current routine practice is to ensure the early identification of PSH, and over the short term this requires homogenization and validation of both the nomenclature used and the diagnostic criteria employed – thereby facilitating comparison of the efficacy of future treatments. Early categorization is essential (not all paroxysms share the same clinical features or characteristics), in the same way as work on a systematic and multidisciplinary basis. The protocolization of treatment is crucial, and should be scaled exclusively according to the patient clinical picture. The aim is to ensure early and intensive care in order to prevent complications and optimize the chances for rehabilitation.Conflicts of interestNone." "textoCompletoSecciones" => array:1 [ "secciones" => array:16 [ 0 => array:3 [ "identificador" => "xres1141387" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1072345" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1141386" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1072346" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Question 1. What do we mean by paroxysmal sympathetic hyperactivity?" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Question 2. What are the main characteristics of paroxysmal sympathetic hyperactivity?" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Question 3. What is the incidence and what are the disorders predisposing to paroxysmal sympathetic hyperactivity?" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Question 4. What are the physiopathological bases of paroxysmal sympathetic hyperactivity?" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Question 5. How can a correct diagnosis be established?" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Question 6. Is neuroimaging necessary?" ] 11 => array:2 [ "identificador" => "sec0040" "titulo" => "Question 7. How should the syndrome be treated?" ] 12 => array:2 [ "identificador" => "sec0045" "titulo" => "Question 8. What are the consequences of a lack of diagnosis or adequate management?" ] 13 => array:2 [ "identificador" => "sec0050" "titulo" => "Conclusions and future challenges" ] 14 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflicts of interest" ] 15 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-07-27" "fechaAceptado" => "2017-10-30" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1072345" "palabras" => array:5 [ 0 => "Sympathetic storm" 1 => "Paroxysmal sympathetic hyperactivity" 2 => "Catecholamines" 3 => "Acute brain injury" 4 => "Severe traumatic brain injury" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1072346" "palabras" => array:5 [ 0 => "Tormenta simpática" 1 => "Hiperactividad simpática paroxística" 2 => "Catecolaminas" 3 => "Lesión cerebral aguda" 4 => "Traumatismo craneoencefálico grave" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Paroxysmal sympathetic hyperactivity (PSH) is a potentially life-threatening neurological emergency secondary to multiple acute acquired brain injuries. It is clinically characterized by the cyclic and simultaneous appearance of signs and symptoms secondary to exacerbated sympathetic discharge. The diagnosis is based on the clinical findings, and high alert rates are required. No widely available and validated homogeneous diagnostic criteria have been established to date. There have been recent consensus attempts to shed light on this obscure phenomenon. Its physiopathology is complex and has not been fully clarified. However, the excitation-inhibition model is the theory that best explains the different aspects of this condition, including the response to treatment with the available drugs. The key therapeutic references are the early recognition of the disorder, avoiding secondary injuries and the triggering of paroxysms. Once sympathetic crises occur, they must be peremptorily aborted and prevented. The later the syndrome is recognized, the poorer the patient outcome." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La hiperactividad simpática paroxística es una urgencia neurológica potencialmente letal secundaria a múltiples lesiones cerebrales agudas adquiridas. Se caracteriza por rasgos clínicos de aparición cíclica y simultánea, consecuencia de una descarga simpática exacerbada. El diagnóstico es clínico, requiriendo elevados índices de alerta. Actualmente no existen criterios diagnósticos homogéneos que estén ampliamente difundidos y validados. El consenso reciente intenta arrojar luz sobre este oscuro panorama. Su fisiopatología es compleja y aún no ha sido elucidada con certeza; sin embargo, la teoría basada en el modelo excitación-inhibición es la que mejor explica los distintos aspectos de esta entidad, incluyendo la respuesta a la terapia con los fármacos disponibles. Los pilares terapéuticos se asientan sobre el reconocimiento precoz, evitar insultos secundarios y el desencadenamiento de los paroxismos. De ocurrir crisis simpáticas, es que estas se aborten de forma perentoria y que se prevengan. Cuanto más tarde en reconocerse el síndrome, peores serán los resultados." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Godoy DA, Panhke P, Guerrero Suarez PD, Murillo-Cabezas F. Hiperactividad simpática paroxística: una entidad que no debería pasar desapercibida. Med Intensiva. 2019;43:35–43." ] ] "multimedia" => array:9 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 838 "Ancho" => 1500 "Tamanyo" => 64204 ] ] "descripcion" => array:1 [ "en" => "Sudden variation in vital signs and onset of perspiration during a sympathetic paroxysm episode in a patient with diffuse axonal damage on performing a waking test. HR: heart rate; RF: respiratory frequency; SBP: systolic blood pressure; Temp: temperature." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 648 "Ancho" => 1333 "Tamanyo" => 26199 ] ] "descripcion" => array:1 [ "en" => "Evolutive stages of paroxysmal sympathetic hyperactivity. Source: Hughes and Rabinstein.<a class="elsevierStyleCrossRef" href="#bib0255">8</a>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 721 "Ancho" => 1508 "Tamanyo" => 66989 ] ] "descripcion" => array:1 [ "en" => "Disorders predisposing to the development of paroxysmal sympathetic hyperactivity. CVA: cerebrovascular accident; TBI: traumatic brain injury. Source: Perkes et al.<a class="elsevierStyleCrossRef" href="#bib0225">2</a>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 2691 "Ancho" => 1600 "Tamanyo" => 275389 ] ] "descripcion" => array:1 [ "en" => "Disconnection theories: A. Conventional. B. Excitation-inhibition model. Source: Baguley.<a class="elsevierStyleCrossRef" href="#bib0340">25</a>" ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 3926 "Ancho" => 3081 "Tamanyo" => 595255 ] ] "descripcion" => array:1 [ "en" => "Management algorithm for paroxysmal sympathetic hyperactivity. ABC of resuscitation: permeable airway, oxygenation and adequate ventilation, stable hemodynamic conditions. Comment: haloperidol and chlorpromazine are to be avoided, due to their antidopaminergic effects that exacerbate or worsen PSH. d: day; mg: milligrams; μg: micrograms; g: grams; IV: intravenous; PO: oral route." ] ] 5 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diencephalic seizures \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Brainstem attack \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Central autonomic dysregulation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hyperadrenergic state \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Midbrain syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Decerebration tonic spasms \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cerebellar tonic discharges \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sympathetic adrenal response \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Autonomic dysfunction syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypothalamic-midbrain dysregulation syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dysautonomy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hyperpyrexia with prolonged muscle contraction \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Autonomic storm \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sympathetic storm \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Paroxysmal autonomic instability with dystonia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Paroxysmal autonomic dysregulation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Paroxysmal sympathetic hyperactivity \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1947751.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Different forms of paroxysmal sympathetic hyperactivity (PSH) nomenclature over time." ] ] 6 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bacteremia, sepsis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Obstruction of the airway \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypoxemia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Severe hypercapnia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypoglycemia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Seizures \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Neurological deterioration (intracranial hypertension, bleeding, edema, hydrocephalus) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pulmonary thromboembolism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Thyroid storm \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acute myocardial infarction \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alcohol or drug withdrawal \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sedation withdrawal syndrome, opioids \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Malignant neuroleptic syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Serotoninergic syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hyperthermia of central origin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Malignant hyperthermia \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1947753.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Disorders sharing signs or symptoms with paroxysmal sympathetic hyperactivity." ] ] 7 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "CFS: Clinical Features Severity scale; DLT: Diagnosis Likelihood Tool; PSH: paroxysmal sympathetic hyperactivity.Source: Baguley et al.<a class="elsevierStyleCrossRef" href="#bib0360">29</a>" "tablatextoimagen" => array:4 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " colspan="6" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Clinical Features Severity scale (CFS)</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">0 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">1 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">3 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Score \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100–119 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">120–139 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>140 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">RF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18–23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24–29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SBP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><140 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">140–159 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">160–179 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>180 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Temperature \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">37–37.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">38–38.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Perspiration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Null \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mild \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Postures \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Null \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mild \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CSF subtotal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1947752.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Type and intensity of hypertonicity during the episode \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " rowspan="4" align="left" valign="top">Severity of the clinical presentation</td><td class="td" title="table-entry " align="left" valign="top">Null \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mild \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1–6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7–12 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>13 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1947754.png" ] ] 2 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diagnosis Likelihood Tool (DLT) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Simultaneity of the clinical manifestations \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Paroxysmal presentation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sympathetic hyperactivity in response to non-painful stimuli \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Persistence of the clinical manifestations ≥3 consecutive days \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Persistence of the clinical manifestations ≥2 weeks post-injury \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Persistence of the clinical manifestations despite treatment of alternative diagnoses \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Treatment for reducing features of sympathetic hyperactivity \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">≥2 daily episodes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Absence of parasympathetic clinical manifestations during the episode \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Absence of other causes explaining the clinical manifestations \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">History of acquired brain damage \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">(1 point for each clinical presentation) DLT subtotal \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1947755.png" ] ] 3 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Combination total (CFS+DLT) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Probability of diagnosis of PSH</td><td class="td" title="table-entry " align="left" valign="top">Improbable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Possible \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8–16 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Probable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>17 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1947750.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Diagnostic scale suggested by expert consensus." ] ] 8 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Source: Leclercq et al.<a class="elsevierStyleCrossRef" href="#bib0385">34</a>; Tang et al.<a class="elsevierStyleCrossRef" href="#bib0390">35</a>; Rabibstein and Benarroch.<a class="elsevierStyleCrossRef" href="#bib0395">36</a>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drug \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mechanism \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mechanism of action \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Starting dose \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Frequency \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Symptoms treated \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Propranolol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Non-selective beta-blocker \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Peripheral reduction of catecholamine effect \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40mg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Every 12h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hypertension, tachycardia, fever \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Morphine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mu opioid agonist \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Central and peripheral vagal modulation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1–8mg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Conditioned to onset of PSH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tachycardia, peripheral vasodilatation, allodynia response \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baclofen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Specific GABA agonist \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Central \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5mg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Every 8h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pain, clonus, stiffness \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gabapentin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">GABA agonist \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Central \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">300mg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Every 8h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Spasticity, allodynia response \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Benzodiazepines \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">GABA agonist \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Central \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Depends on the drug used \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Agitation, hypertension, tachycardia, postures \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bromocriptine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">D2 dopaminergic agonist \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hypothalamic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.25mg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Every 12h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Dystonias, fever, postures \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Clonidine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">α2, Agonist \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reduces central sympathetic discharge \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.1–0.3mg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Every 12h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hypertension \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dexmedetomidine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">α2, Agonist \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reduces central sympathetic discharge \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2μg/kg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Every 1h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hypertension, agitation, tachycardia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dantrolene \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reduces muscle contraction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Peripheral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.25–2mg/kg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Every 6–12h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Muscle stiffness, anomalous postures \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1947756.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Drugs used for the treatment of paroxysmal sympathetic hyperactivity." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:43 [ 0 => array:3 [ "identificador" => "bib0220" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diencephalic autonomic epilepsy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "W. 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Paroxysmal sympathetic hyperactivity: An entity to keep in mind

Hiperactividad simpática paroxística: una entidad que no debería pasar desapercibida

D.A. Godoya,b,

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dagodoytorres@yahoo.com.ar

Corresponding author.

, P. Panhkec, P.D. Guerrero Suarezd, F. Murillo-Cabezase

a Unidad de Cuidados Neurointensivos, Sanatorio Pasteur, Catamarca, Argentina

b Unidad de Terapia Intensiva, Hospital San Juan Bautista, Catamarca, Argentina

c Shock Room, Hospital Municipal de Urgencias, Córdoba, Argentina

d Departamento de Neurocirugía, Centro Médico ISSEMyM, Toluca, Mexico

e Unidad de Gestión Clínica de Cuidados Intensivos, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain

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and different terms have been used to describe them&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;6</span></a> Sympathetic alterations predominate in some cases and parasympathetic alterations in others&#44; though both the sympathetic and the parasympathetic autonomic nervous system can be more or less equally affected in some patients&#46; This circumstance tends to cause confusion&#44; making it difficult to adequately study the disease<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#44;6</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The term &#8220;paroxysmal sympathetic hyperactivity&#8221; &#40;PSH&#41; has recently been introduced&#44; summarizing the main characteristics of the syndrome&#44; which results from overactivity of only the sympathetic nervous system&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;5&#44;7&#44;8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Paroxysmal sympathetic hyperactivity is a genuine neurological emergency that may go undetected if not taken into account&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;8</span></a> The diagnosis is mainly established on an exclusion basis&#44; ruling out other possible diagnoses&#44; and requires a strong degree of suspicion&#46; Failure to adequately detect and treat the condition is associated to high mortality-morbidity rates&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The main objective of this study is to offer simple and practical answers to questions referred to the correct identification and management of the disease&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Question 1&#46; What do we mean by paroxysmal sympathetic hyperactivity&#63;</span><p id="par0030" class="elsevierStylePara elsevierViewall">Paroxysmal sympathetic hyperactivity comprises a series of signs and symptoms reflecting exacerbated sympathetic activity&#44; including&#58; tachycardia&#44; arterial hypertension&#44; tachypnea&#44; hyperthermia&#44; generalized perspiration&#44; anomalous motor activity &#40;dystonia&#44; muscle stiffness&#44; extension&#41; and mechanical ventilator maladjustment&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;8</span></a> These clinical features moreover manifest simultaneously&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;8</span></a> The number of signs or symptoms is closely correlated to the ultimate outcome&#44;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">4</span></a> with more profuse manifestations being associated to a poorer prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">4</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Paroxysmal sympathetic hyperactivity is not a primary disorder but always develops as a result of brain injuries of variable nature and severity&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;8</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Question 2&#46; What are the main characteristics of paroxysmal sympathetic hyperactivity&#63;</span><p id="par0040" class="elsevierStylePara elsevierViewall">Paroxysmal sympathetic hyperactivity manifests abruptly in cyclic episodes&#44; either spontaneously or in response to stimuli such as pain&#44; bathing&#44; the aspiration of secretions&#44; exposure to light&#44; touch or physiotherapy&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;8</span></a> Sympathetic hyperactivity can manifest at any time in the course of the disorder that causes it&#44; though it is usually detected after the first week&#44; coinciding with a decrease or the suspension of deep sedoanalgesia<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;8</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The literature indicates that in most instances the diagnosis is made one week after patient admission&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">8</span></a> The paroxysms appear 3&#8211;5 times a day and last an average of 30<span class="elsevierStyleHsp" style=""></span>min&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;8</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">The syndrome has three evolutive stages&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">8</span></a> Hyperacute phase I covers the first week&#44; during which the expression of brain damage is maximum&#46; The patient is generally unstable and intensive treatment is provided&#44; including generally deep sedation and analgesia&#46; As a result&#44; the diagnosis cannot be established in this stage&#44; unless a waking test is made for some reason or the patient accidentally emerges from anesthesia&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">8</span></a> In phase II the syndrome &#8211; with the aforementioned features &#8211; is fully expressed&#46; This stage typically extends to two and a half months after the causal injury &#40;day 74&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Cessation of the perspiration episodes marks the end of stage II&#44;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">8</span></a> which is followed by stage III&#46; The latter comprises the rehabilitation period and can last for years &#8211; though the episodes in this case are generally less frequent and of lesser intensity and duration<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">8</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Question 3&#46; What is the incidence and what are the disorders predisposing to paroxysmal sympathetic hyperactivity&#63;</span><p id="par0055" class="elsevierStylePara elsevierViewall">The reported incidence of PSH ranges from 8&#37; to 33&#37;&#44;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;8</span></a> depending on the series and the underlying etiology of the disease&#46; The disease can manifest in both children and adults&#44;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;8</span></a> and has no particular age or gender predilection&#46; A number of conditions predispose to the development of PSH&#44; the most common being traumatic brain injury &#40;80&#37;&#41; in its diffuse axonal damage presentation&#44;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">9&#8211;14</span></a> followed by post-cardiac arrest anoxic-ischemic encephalopathy &#40;10&#37;&#41; and cerebrovascular accident &#40;CVA&#41; &#40;5&#46;5&#37;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;8</span></a> In relation to CVA&#44; spontaneous intraparenchymal bleeding of the basal nuclei&#44; thalamus and cerebellar vermis&#44; with or without ventricular collapse&#44; is seen to predominate&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">15&#44;16</span></a> There have also been reports of PSH in patients with severe subarachnoid hemorrhage&#44;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">17&#44;18</span></a> ischemic CVA&#44; cerebral venous thrombosis&#44; encephalitis and cerebral lipid embolism<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;5&#44;19&#44;20</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Question 4&#46; What are the physiopathological bases of paroxysmal sympathetic hyperactivity&#63;</span><p id="par0060" class="elsevierStylePara elsevierViewall">The main intervening element is the autonomic nervous system &#40;ANS&#41; or neurovegetative system&#44; which is in charge of regulating involuntary actions through its three main components&#58; sympathetic&#44; parasympathetic and enteric&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">21</span></a> The ANS is essentially an efferent system&#46; It receives information from the internal environment&#44; glands and organs through a complex network located in the spinal cord&#44; brainstem&#44; diencephalon&#44; hypothalamus&#44; limbic system and certain areas of the brain cortex&#44; and subsequently transmits impulses toward the periphery&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">21</span></a> In this way the ANS regulates heart rate&#44; respiratory frequency&#44; pupil diameter and blood vessel caliber&#44; smooth muscle contraction&#44; salivation&#44; perspiration&#44; sexual function&#44; endocrine and exocrine gland secretion&#44; and digestion&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">21</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The sympathetic nervous system is composed of preaortic and pre- and paravertebral ganglionic networks&#46; Catecholamines are the main intervening neurotransmitters&#44; and are carefully regulated and balanced through excitatory and inhibitory impulses&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">21</span></a> When this balance is altered as a consequence of brain damage&#44; catecholamine release becomes excessive&#44; thereby giving rise to the clinical features typical of PSH&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">22&#44;23</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Why do imbalances resulting in catecholamine elevation during sympathetic paroxysm occur&#63;</span> The precise underlying physiopathology remains unclear&#46; The syndrome was initially attributed to seizures or endocranial hypertension&#46; Both conditions were discarded&#44; however&#44; since there is no close correlation between these two disorders and the presence of the syndrome&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;5&#44;24&#44;25</span></a> The absence of seizure activity as evidenced by the electroencephalogram &#40;EEG&#41; during sympathetic paroxysms has been clearly confirmed&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#44;24&#44;25</span></a> On the other hand&#44; a rise in intracranial pressure &#40;ICP&#41; is more a consequence than a cause of the syndrome&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;5</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Following brain damage there is an immediate metabolic and inflammatory response&#44; with activation of the ANS&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">26</span></a> This in turn induces tachycardia&#44; arterial hypertension and the redistribution of blood flow toward the brain&#44; heart and adrenal glands&#44; in order to ensure the availability of oxygen and preserve the physiological functions of the vital organs of the body&#46; The parasympathetic system in turn attempts to restore homeostasis by reducing the effects of sympathetic hyperactivity&#46; However&#44; when this parasympathetic feedback mechanism fails&#44; sympathetic activity is disinhibited&#44; hyperactivity results&#44; and PSH ultimately develops&#46; Two hypotheses have been proposed to explain this phenomenon<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">24&#44;25</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">The conventional theory of disconnection &#8211; whether structural &#40;anatomical lesion&#41; or functional &#40;imbalanced neurotransmitter release&#41; &#8211; postulates that sympathetic excitatory centers located in the diencephalon and upper region of the brainstem become freed from higher cortical-subcortical control&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">24</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">The excitation-inhibition ratio model in turn postulates that the centers located in the brainstem and diencephalon are inhibitory by nature&#46; In this respect&#44; they limit amplification and sensitization of the afferent sensory information coming from the spinal cord&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">24&#44;25</span></a> In this model&#44; PSH is referred to as allodynia &#8211; a term that defines a sensitization process occurring in the dorsal horn of the spinal cord&#44; in which non-painful stimuli are perceived as painful&#44; including the aspiration of secretions&#44; body rotation&#44; bathing&#44; constipation and urinary retention&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">24&#44;25</span></a> At the same time&#44; painful stimuli become magnified in intensity&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">On the other hand&#44; the excitation-inhibition ratio model helps explain the triggering of PSH in response to environmental stimuli&#44; as well as the response to drugs used to control the disorder&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">24&#44;25</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Question 5&#46; How can a correct diagnosis be established&#63;</span><p id="par0095" class="elsevierStylePara elsevierViewall">A strong degree of suspicion is required&#44; particularly when in the context of acquired brain damage&#44; during therapeutic de-escalation&#44; &#8220;awakening from coma&#8221;&#44; or in the rehabilitation phase&#44; the patient suffers simultaneous and transient paroxysmal episodes of sympathetic hyperactivity&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#44;3&#44;6&#8211;8&#44;27</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">The predominant signs and symptoms are&#58; tachycardia &#40;98&#37;&#41;&#44; arterial hypertension &#40;72&#37;&#41;&#44; excessive perspiration &#40;79&#37;&#41;&#44; fever in the absence of an infectious focus &#40;79&#37;&#41;&#44; tachypnea &#40;85&#37;&#41;&#44; extensor body posture &#40;38&#37;&#41;&#44; dystonia &#40;38&#37;&#41;&#44; stiffness or spasticity &#40;44&#37;&#41;&#46; Less frequent manifestations are&#58; intermittent dilation of the pupils&#44; diminished consciousness&#44; hair erection&#44; excitation and mechanical ventilator maladjustment&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#44;8</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">No complementary tests are available for confirming the diagnosis of PSH&#46; The diagnosis is eminently clinical&#44; and other situations involving similar clinical features therefore need to be ruled out<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#44;3&#44;6&#8211;8</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">Although the syndrome has been known for over 60 years&#44; its diagnostic criteria are not homogeneous and have not been validated&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;8</span></a> Different numbers and combinations of signs have been used to confirm the existence of PSH&#44;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#44;28</span></a> and only recently has expert consensus established its definition and the criteria to be used&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">29</span></a> Following a systematic review of the literature&#44; a scale was developed based on the combination of a score that assesses the presence and severity of the clinical parameters &#40;Clinical Features Severity &#91;CFS&#93;&#41;&#46; This score is added to another score that assesses the characteristics of the episodes &#40;frequency&#44; duration&#44; persistence over time&#44; simultaneity&#44; etc&#46;&#41;&#44; known as the Diagnosis Likelihood Tool &#40;DLT&#41;<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">29&#44;30</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; The final score obtained from the sum of these two scales allows us to calculate the probability of suffering PSH with increased precision&#44; though its validation remains pending&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">Although the catecholamine or other hormonal axis values for diagnosing the syndrome have not been defined&#44; a recent study has generated the first proof of catecholamine elevation and&#44; to a lesser extent&#44; increased adrenocortical response&#44; in individuals with PSH versus controls without the syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">23</span></a> These findings provide bases for warranting the current nomenclature referred to the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">29</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Question 6&#46; Is neuroimaging necessary&#63;</span><p id="par0120" class="elsevierStylePara elsevierViewall">Neuroimaging is not essential for diagnosing PSH&#46; Nevertheless&#44; it contributes to maintain a high level of suspicion by revealing the type of brain injury in the initial imaging study &#40;focal or diffuse&#41;&#44; its morphology &#40;intracerebral hemorrhage&#44; ischemia&#44; contusions&#44; extraaxial hematomas&#44; etc&#46;&#41;&#44; the anatomical location&#44; and the extent of the primary damage&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">31&#8211;33</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Computed tomography &#40;CT&#41; is undoubtedly the imaging tool of choice in the acute phase&#46; In more stable patients&#44; without a need for multiple monitoring procedures&#44; magnetic resonance imaging &#40;MRI&#41; with or without tractography can be used to more precisely define the degree of anatomical involvement &#8211; particularly as regards those anatomical structures more closely related to the development of PSH&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">34</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Question 7&#46; How should the syndrome be treated&#63;</span><p id="par0130" class="elsevierStylePara elsevierViewall">Preventing PSH would be the ideal strategy&#46; However&#44; to date no measures in this regard have been successful&#46; A recent retrospective study with important methodological limitations has indicated that the use of dexmedetomidine&#44; versus the traditionally used sedatives &#40;midazolam or propofol&#41;&#44; in brain trauma patients subjected to surgery could reduce the incidence of PSH&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">35</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">As in any neurological emergency&#44; the first aim of management is to ensure cardiorespiratory stability by means of the ABC of resuscitation in combination with the measures needed to detect and correct secondary lesions&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;5&#44;36&#8211;39</span></a> Adequate nutrition and a correct water-electrolyte balance are very important assisting measures in patients with PSH&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">39</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">The existing drug strategies for the specific management of PSH are fundamented upon case series&#44; most of which are retrospective and non-randomized&#46; The quality of the evidence on the efficacy of the proposed measures is therefore poor&#46; Likewise&#44; it is important to note the lack of studies demonstrating the preference of one drug substance versus another&#46; Nevertheless&#44; the experience and the literature indicate that &#8220;drug combinations&#8221; are generally required&#44; and that these should be evaluated through the so-called &#8220;trial and error&#8221; approach&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">3&#44;5&#44;20&#44;36&#44;38</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">In order to control excessive sympathetic activity or its consequences&#44; it is important to orientate treatment according to the currently accepted physiopathology of PSH&#46; In this regard&#44; the paroxysms can be mitigated through three main approaches&#58; &#40;a&#41; inhibition of central sympathetic flow&#59; &#40;b&#41; inhibition of afferent sensory processes &#40;preventing the development of allodynia&#41;&#59; and &#40;c&#41; blockade of effector organ end response&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">3&#44;5&#44;20&#44;36&#8211;38</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">At present&#44; optimized treatment &#40;effectiveness &#8211; adverse reactions &#8211; interactions&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41; seeks the following&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#41;</span><p id="par0155" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Abort crises or suspend symptoms</span>&#58; The aim here is to control the episode immediately in order to prevent adverse effects such as cardiac overload&#44; arrhythmias&#44; dehydration&#44; muscle loss&#44; contractures or delayed recovery from contributing to increase patient morbidity&#46; The drugs used are characterized by rapid onset of action and a short half-life&#44; and the choice of substance depends on the dominant symptom in each case&#46; The indicated drugs include morphine&#44; propranolol and short-acting benzodiazepines&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">3&#44;5&#44;20&#44;36&#8211;38</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#41;</span><p id="par0160" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Prevention of paroxysms</span>&#58; Treatment in this regard seeks to reduce the frequency&#44; duration and intensity of the symptoms&#44; and is indicated in combination with the aforementioned therapy&#46; The drugs used include nonselective beta-blockers &#40;propranolol&#41;&#44; &#945;2-agonists &#40;clonidine and dexmedetomidine in some groups of patients<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">35</span></a>&#41;&#44; bromocriptine&#44; baclofen&#44; gabapentin and long-acting benzodiazepines&#46;<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">36&#44;37</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">3&#41;</span><p id="par0165" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Refractory PSH&#58;</span> When sympathetic hyperactivity persists despite the abovementioned treatments&#44; with the risk of causing secondary brain damage&#44; brain edema&#44; lung edema&#44; myocardial infarction&#44; or catecholaminergic myocarditis including sudden death&#44; use is made of drugs in continuous intravenous infusion&#44; such as benzodiazepines&#44; propofol&#44; opioids or dexmedetomidine&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">38</span></a></p></li></ul></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0170" class="elsevierStylePara elsevierViewall">The effective clinical management of patients with PSH requires a clear understanding of the available treatment options&#44; their efficacy&#44; dosing characteristics&#44; half-life&#44; administration route&#44; interactions and adverse effects&#46; Treatment protocolization is therefore essential&#46; A number of algorithms have been published in this respect&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">3&#44;40</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Since on one hand not all paroxysms are the same in terms of severity&#44; frequency or duration&#44; and on the other hand the available drug substances are not without potential toxic effects&#44; we consider it important to categorize the episodes in order to use the treatment combination offering the best risk-benefit ratio&#46; We thus recommend using the CFS<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>DLT diagnostic scale and classifying the patients into four possible groups &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#58;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0180" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Group A</span>&#160;&#60;&#160;8 points&#46; Treatment targeted to the dominant symptom&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Group B</span>&#160;8&#8211;16 points&#46; Symptomatic<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>preventive treatment&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Group C</span>&#160;&#62;&#160;17 points&#46; Symptomatic<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>preventive treatment<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>gabapentin or dantrolene or baclofen&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Refractory group</span>&#58; Continuous intravenous infusion of propofol&#44; fentanil&#44; midazolam or dexmedetomidine&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Question 8&#46; What are the consequences of a lack of diagnosis or adequate management&#63;</span><p id="par0200" class="elsevierStylePara elsevierViewall">Paroxysmal sympathetic hyperactivity episodes can be intense and prolonged&#44; and can occur several times a day&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;6&#44;41</span></a> The number of symptoms rather than the duration of PSH is the most important severity indicator&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">4</span></a> Arterial hypertension&#44; fever&#44; hypoxemia&#44; hypercapnia and hyperglycemia can cause secondary brain damage&#44; and are the main causes of a poor prognosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;6</span></a> Paroxysmal sympathetic hyperactivity in turn induces a hypermetabolic state&#44; with hypercatabolism and inflammation&#44; and increased vulnerability to infections&#44; sepsis and weight loss&#44; which in turn are associated to increased morbidity&#44; longer hospital stay and slower recovery&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;6&#44;20</span></a> The marked and sustained increase in catecholamine levels predisposes to the development of myocardiopathy&#44; lung edema&#44; arrhythmias&#44; and cardiac and multisystemic dysfunction&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;8&#44;20</span></a> An early diagnosis and optimized treatment of PSH are crucial in order to facilitate patient recovery and avoid permanent disabilities secondary to heterotopic ossification&#44; spastic stiffness&#44; body malpositioning and profound neurocognitive disturbances&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">2&#8211;8&#44;20</span></a> The early start of specific symptoms therapy is believed to reduce the complications rate&#44; shorten stay in the Intensive Care Unit &#40;ICU&#41; and facilitate recovery&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">18</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Diagnostic and&#47;or therapeutic delays in PSH can have devastating consequences for patient recovery&#46; However&#44; on comparing the post-rehabilitation course of patients with and without PSH&#44; functional condition at discharge shows no statistically significant differences as determined from the Functional Independence Measure&#44; Disability Rating Scale and Glasgow Outcome Scale &#8211; though the probability and degree of recovery is greater in those without PSH&#46;<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">42&#44;43</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">The expectable course of recovery from traumatic brain damage extends from acute management to rehabilitation and reinsertion in the community&#46; The effects of PSH can alter the course of rehabilitation and delay or impede maximum patient recovery&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">43</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conclusions and future challenges</span><p id="par0215" class="elsevierStylePara elsevierViewall">Paroxysmal sympathetic hyperactivity is a genuine and potentially fatal neurological emergency&#46; The diagnosis is based on the clinical findings&#59; as a result&#44; the professionals in charge of the care of neurocritical patients must be able to detect the syndrome and require adequate training&#46; The greatest challenge in current routine practice is to ensure the early identification of PSH&#44; and over the short term this requires homogenization and validation of both the nomenclature used and the diagnostic criteria employed &#8211; thereby facilitating comparison of the efficacy of future treatments&#46; Early categorization is essential &#40;not all paroxysms share the same clinical features or characteristics&#41;&#44; in the same way as work on a systematic and multidisciplinary basis&#46; The protocolization of treatment is crucial&#44; and should be scaled exclusively according to the patient clinical picture&#46; The aim is to ensure early and intensive care in order to prevent complications and optimize the chances for rehabilitation&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflicts of interest</span><p id="par0220" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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          "titulo" => "Introduction"
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          "titulo" => "Question 1&#46; What do we mean by paroxysmal sympathetic hyperactivity&#63;"
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          "titulo" => "Question 2&#46; What are the main characteristics of paroxysmal sympathetic hyperactivity&#63;"
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          "titulo" => "Question 3&#46; What is the incidence and what are the disorders predisposing to paroxysmal sympathetic hyperactivity&#63;"
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          "titulo" => "Question 4&#46; What are the physiopathological bases of paroxysmal sympathetic hyperactivity&#63;"
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          "titulo" => "Question 5&#46; How can a correct diagnosis be established&#63;"
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          "titulo" => "Question 7&#46; How should the syndrome be treated&#63;"
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          "titulo" => "Question 8&#46; What are the consequences of a lack of diagnosis or adequate management&#63;"
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          "titulo" => "Conclusions and future challenges"
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          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2017-07-27"
    "fechaAceptado" => "2017-10-30"
    "PalabrasClave" => array:2 [
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1072345"
          "palabras" => array:5 [
            0 => "Sympathetic storm"
            1 => "Paroxysmal sympathetic hyperactivity"
            2 => "Catecholamines"
            3 => "Acute brain injury"
            4 => "Severe traumatic brain injury"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1072346"
          "palabras" => array:5 [
            0 => "Tormenta simp&#225;tica"
            1 => "Hiperactividad simp&#225;tica parox&#237;stica"
            2 => "Catecolaminas"
            3 => "Lesi&#243;n cerebral aguda"
            4 => "Traumatismo craneoencef&#225;lico grave"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Paroxysmal sympathetic hyperactivity &#40;PSH&#41; is a potentially life-threatening neurological emergency secondary to multiple acute acquired brain injuries&#46; It is clinically characterized by the cyclic and simultaneous appearance of signs and symptoms secondary to exacerbated sympathetic discharge&#46; The diagnosis is based on the clinical findings&#44; and high alert rates are required&#46; No widely available and validated homogeneous diagnostic criteria have been established to date&#46; There have been recent consensus attempts to shed light on this obscure phenomenon&#46; Its physiopathology is complex and has not been fully clarified&#46; However&#44; the excitation-inhibition model is the theory that best explains the different aspects of this condition&#44; including the response to treatment with the available drugs&#46; The key therapeutic references are the early recognition of the disorder&#44; avoiding secondary injuries and the triggering of paroxysms&#46; Once sympathetic crises occur&#44; they must be peremptorily aborted and prevented&#46; The later the syndrome is recognized&#44; the poorer the patient outcome&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La hiperactividad simp&#225;tica parox&#237;stica es una urgencia neurol&#243;gica potencialmente letal secundaria a m&#250;ltiples lesiones cerebrales agudas adquiridas&#46; Se caracteriza por rasgos cl&#237;nicos de aparici&#243;n c&#237;clica y simult&#225;nea&#44; consecuencia de una descarga simp&#225;tica exacerbada&#46; El diagn&#243;stico es cl&#237;nico&#44; requiriendo elevados &#237;ndices de alerta&#46; Actualmente no existen criterios diagn&#243;sticos homog&#233;neos que est&#233;n ampliamente difundidos y validados&#46; El consenso reciente intenta arrojar luz sobre este oscuro panorama&#46; Su fisiopatolog&#237;a es compleja y a&#250;n no ha sido elucidada con certeza&#59; sin embargo&#44; la teor&#237;a basada en el modelo excitaci&#243;n-inhibici&#243;n es la que mejor explica los distintos aspectos de esta entidad&#44; incluyendo la respuesta a la terapia con los f&#225;rmacos disponibles&#46; Los pilares terap&#233;uticos se asientan sobre el reconocimiento precoz&#44; evitar insultos secundarios y el desencadenamiento de los paroxismos&#46; De ocurrir crisis simp&#225;ticas&#44; es que estas se aborten de forma perentoria y que se prevengan&#46; Cuanto m&#225;s tarde en reconocerse el s&#237;ndrome&#44; peores ser&#225;n los resultados&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Godoy DA&#44; Panhke P&#44; Guerrero Suarez PD&#44; Murillo-Cabezas F&#46; Hiperactividad simp&#225;tica parox&#237;stica&#58; una entidad que no deber&#237;a pasar desapercibida&#46; Med Intensiva&#46; 2019&#59;43&#58;35&#8211;43&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Sudden variation in vital signs and onset of perspiration during a sympathetic paroxysm episode in a patient with diffuse axonal damage on performing a waking test&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">HR&#58; heart rate&#59; RF&#58; respiratory frequency&#59; SBP&#58; systolic blood pressure&#59; Temp&#58; temperature&#46;</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Evolutive stages of paroxysmal sympathetic hyperactivity&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Hughes and Rabinstein&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">8</span></a></p>"
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        "mostrarFloat" => true
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Disorders predisposing to the development of paroxysmal sympathetic hyperactivity&#46;</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">CVA&#58; cerebrovascular accident&#59; TBI&#58; traumatic brain injury&#46;</p> <p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Perkes et al&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">2</span></a></p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Disconnection theories&#58; A&#46; Conventional&#46; B&#46; Excitation-inhibition model&#46;</p> <p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Baguley&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">25</span></a></p>"
        ]
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      4 => array:7 [
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        "mostrarFloat" => true
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        "figura" => array:1 [
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Management algorithm for paroxysmal sympathetic hyperactivity&#46;</p> <p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">ABC of resuscitation&#58; permeable airway&#44; oxygenation and adequate ventilation&#44; stable hemodynamic conditions&#46;</p> <p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Comment&#58; haloperidol and chlorpromazine are to be avoided&#44; due to their antidopaminergic effects that exacerbate or worsen PSH&#46;</p> <p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">d&#58; day&#59; mg&#58; milligrams&#59; &#956;g&#58; micrograms&#59; g&#58; grams&#59; IV&#58; intravenous&#59; PO&#58; oral route&#46;</p>"
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        "tabla" => array:1 [
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diencephalic seizures&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Brainstem attack&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Central autonomic dysregulation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hyperadrenergic state&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Midbrain syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Decerebration tonic spasms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cerebellar tonic discharges&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sympathetic adrenal response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Autonomic dysfunction syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypothalamic-midbrain dysregulation syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dysautonomy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hyperpyrexia with prolonged muscle contraction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Autonomic storm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sympathetic storm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Paroxysmal autonomic instability with dystonia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Paroxysmal autonomic dysregulation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Paroxysmal sympathetic hyperactivity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Different forms of paroxysmal sympathetic hyperactivity &#40;PSH&#41; nomenclature over time&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bacteremia&#44; sepsis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Obstruction of the airway&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypoxemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Severe hypercapnia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypoglycemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Seizures&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Neurological deterioration &#40;intracranial hypertension&#44; bleeding&#44; edema&#44; hydrocephalus&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pulmonary thromboembolism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Thyroid storm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Acute myocardial infarction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Alcohol or drug withdrawal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sedation withdrawal syndrome&#44; opioids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Malignant neuroleptic syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Serotoninergic syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hyperthermia of central origin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Malignant hyperthermia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">CFS&#58; Clinical Features Severity scale&#59; DLT&#58; Diagnosis Likelihood Tool&#59; PSH&#58; paroxysmal sympathetic hyperactivity&#46;</p><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Baguley et al&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">29</span></a></p>"
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;140&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#8211;23&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SBP&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;180&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Temperature&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">37&#8211;37&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">38&#8211;38&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Perspiration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Null&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Mild&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Postures&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Null&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Mild&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CSF subtotal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1947752.png"
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            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Type and intensity of hypertonicity during the episode&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " rowspan="4" align="left" valign="top">Severity of the clinical presentation</td><td class="td" title="table-entry  " align="left" valign="top">Null&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mild&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#8211;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#8211;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1947754.png"
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            ]
            2 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diagnosis Likelihood Tool &#40;DLT&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Simultaneity of the clinical manifestations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Paroxysmal presentation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sympathetic hyperactivity in response to non-painful stimuli&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Persistence of the clinical manifestations &#8805;3 consecutive days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Persistence of the clinical manifestations &#8805;2 weeks post-injury&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Persistence of the clinical manifestations despite treatment of alternative diagnoses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Treatment for reducing features of sympathetic hyperactivity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#8805;2 daily episodes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Absence of parasympathetic clinical manifestations during the episode&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Absence of other causes explaining the clinical manifestations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">History of acquired brain damage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#40;1 point for each clinical presentation&#41;<br>DLT subtotal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1947755.png"
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            ]
            3 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Combination total &#40;CFS<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>DLT&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " rowspan="3" align="left" valign="top">Probability of diagnosis of PSH</td><td class="td" title="table-entry  " align="left" valign="top">Improbable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Possible&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#8211;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Probable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1947750.png"
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            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Diagnostic scale suggested by expert consensus&#46;</p>"
        ]
      ]
      8 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at4"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Source&#58; Leclercq et al&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">34</span></a>&#59; Tang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">35</span></a>&#59; Rabibstein and Benarroch&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">36</span></a></p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mechanism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mechanism of action&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Starting dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Frequency&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Symptoms treated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Propranolol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Non-selective beta-blocker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Peripheral reduction of catecholamine effect&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Every 12<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hypertension&#44; tachycardia&#44; fever&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Morphine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Mu opioid agonist&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Central and peripheral vagal modulation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#8211;8<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Conditioned to onset of PSH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tachycardia&#44; peripheral vasodilatation&#44; allodynia response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baclofen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Specific GABA agonist&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Central&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Every 8<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Pain&#44; clonus&#44; stiffness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gabapentin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">GABA agonist&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Central&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">300<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Every 8<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Spasticity&#44; allodynia response&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Benzodiazepines&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">GABA agonist&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Central&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Depends on the drug used&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Agitation&#44; hypertension&#44; tachycardia&#44; postures&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bromocriptine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">D<span class="elsevierStyleInf">2</span> dopaminergic agonist&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hypothalamic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;25<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Every 12<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Dystonias&#44; fever&#44; postures&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Clonidine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#945;2&#44; Agonist&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Reduces central sympathetic discharge&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;1&#8211;0&#46;3<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Every 12<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dexmedetomidine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#945;2&#44; Agonist&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Reduces central sympathetic discharge&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Every 1<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hypertension&#44; agitation&#44; tachycardia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Dantrolene&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Reduces muscle contraction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Peripheral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;25&#8211;2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Every 6&#8211;12<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Muscle stiffness&#44; anomalous postures&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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Article information

ISSN: 21735727
Original language: English

DOI:10.1016/j.medine.2018.10.003

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Year/Month	Html	Pdf	Total

2024 November	16	14	30
2024 October	128	100	228
2024 September	158	76	234
2024 August	141	95	236
2024 July	156	95	251
2024 June	146	89	235
2024 May	152	74	226
2024 April	125	93	218
2024 March	170	101	271
2024 February	179	93	272
2024 January	150	78	228
2023 December	180	118	298
2023 November	230	101	331
2023 October	256	116	372
2023 September	217	105	322
2023 August	135	43	178
2023 July	215	69	284
2023 June	152	54	206
2023 May	204	83	287
2023 April	215	88	303
2023 March	205	134	339
2023 February	161	83	244
2023 January	156	80	236
2022 December	190	86	276
2022 November	168	86	254
2022 October	172	87	259
2022 September	156	102	258
2022 August	162	114	276
2022 July	125	73	198
2022 June	119	49	168
2022 May	177	83	260
2022 April	141	95	236
2022 March	170	115	285
2022 February	154	91	245
2022 January	173	136	309
2021 December	182	103	285
2021 November	150	87	237
2021 October	172	118	290
2021 September	141	88	229
2021 August	187	121	308
2021 July	164	77	241
2021 June	214	102	316
2021 May	305	128	433
2021 April	562	367	929
2021 March	366	155	521
2021 February	240	76	316
2021 January	234	101	335
2020 December	247	76	323
2020 November	209	60	269
2020 October	249	100	349
2020 September	300	53	353
2020 August	300	60	360
2020 July	277	53	330
2020 June	278	53	331
2020 May	252	48	300
2020 April	302	70	372
2020 March	181	50	231
2020 February	333	136	469
2020 January	158	87	245
2019 December	207	59	266
2019 November	273	74	347
2019 October	245	57	302
2019 September	229	61	290
2019 August	161	41	202
2019 July	107	41	148
2019 June	72	31	103
2019 May	170	53	223
2019 April	6	12	18
2019 March	0	23	23
2019 February	1	18	19
2019 January	0	6	6

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